1. Technical Field
The disclosure generally relates to compositions and methods for treatment of ischemic disorders, particularly ischemic disorders of the extremities associated with compromised blood flow, such as but not limited to limb ischemia. More particularly, the disclosed method features the identification, isolation, expansion and use of mesodermal-like progenitor cells that bear both the CD34 and M-cadherin markers, as a cell therapy.
2. Description of Related Art
Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arterial blood vessels characterized by the deposition of fatty substances, primarily cholesterol, and subsequent fibrosis that results from a chronic inflammatory response at the site of the deposit in the artery, resulting in plaque deposition on the inner surface of the arterial wall and degenerative changes within it. Atherosclerosis can eventually lead to plaque ruptures and stenosis (narrowing) of the artery and, therefore, an insufficient blood supply (ischemia) to the tissue or organ it supplies. Medical complications due to atherosclerosis are slow to develop and progress but are cumulative.
Coronary artery disease (CAD) (or atherosclerotic heart disease) is the leading cause of death worldwide and is the end result of the accumulation of plaques within the walls of the arteries that supply the myocardium (the muscle of the heart) with oxygen and nutrients. Vulnerable plaques can suddenly rupture causing the formation of a thrombus (clot) that rapidly slows or stops blood flow, leading to death of the tissues fed by the artery in approximately 5 minutes. Such a catastrophic event is known as an infarction. When it occurs in a coronary artery, it results in a myocardial infarction or heart attack. Since atherosclerosis is a body-wide process, similar events occur also in the arteries to the brain, intestines, kidneys, legs, etc. Another event experienced with advanced CAD is claudication from insufficient blood supply to the legs, typically due to a combination of both stenosis and aneurysmal segments narrowed with clots.
Ischemia is an absolute or relative shortage of the blood supply to a part of the body, when the blood supply is not sufficient to provide adequate oxygenation and the nutritional requirement of the tissue. For example myocardial ischemia is a temporary ischemia of the heart muscle and the cause of angina pectoris, whose symptoms result when the ischemic heart muscle does not function optimally or efficiently, but if the blood flow is improved myocardial ischemia can be reversed. Thus one must distinguish between myocardial ischemia and myocardial infarction. Ischemia can result from many things, such as but not limited to tachycardia, atherosclerosis, hypotension, thromboembolism, sickle cell disease, external compression of a blood vessel or even g-forces. While many of these events result in transient ischemia, if complete ischemia is sustained it can result in cell and tissue necrosis and irreversible damage.
Peripheral artery occlusive disease (PAOD), also known as peripheral vascular disease (PVD,) and most commonly referred to as peripheral artery disease (PAD), encompasses diseases caused by the obstruction of peripheral arteries. This obstruction can be a result of atherosclerosis, inflammatory processes leading to stenosis, an embolism or thrombus formation.
PAD is a common circulatory problem in which narrowed arteries reduce blood flow to the limbs. Lower-extremity PAD affects approximately 8 million Americans. Many people with PAD are asymptomatic or have only mild symptoms with only one in 10 experiencing leg pain when walking, thus PAD may be even more common.
PAD often results from a narrowing of arteries in the legs due to arteriosclerosis. When leg arteries are affected, blood flow to the legs and feet is reduced. Some people may refer to this as poor circulation. But when the blood flow to the legs is significantly reduced, people with PAD may experience pain when walking. Thus, as it advances PAD may become disabling and prevent patients from being able to go to work, and greatly diminishes their quality of life.
Thus a clear and outstanding need exists for a method to treat the more severe symptoms of PAD specifically and ischemia in general. The present disclosure describes just such a technology and treatment method based in regenerative medicine.